Ointments, creams, or liquid formulations which include various antifungal agents have been developed for the treatment of tinea or candidiasis and are commercially available. However, these dosage forms have a short duration of effective drug concentration at the application sites and require 2 to 3 applications per day, and therefore patient compliance with treatments using them has been poor. To compensate for this disadvantage, transdermal formulations which include various antifungal agents have been under investigation.
For example, Patent Documents 1 and 2 disclose patches which include antifungal agents blended in an acrylic or a rubber-base adhesive. Patent Document 3 discloses a therapeutic composition for tinea unguium which includes omoconazole nitrate or butenafine hydrochloride blended in a base consisting of a hydrophobic film component and a solvent. Patent Document 4 discloses an external preparation which includes 2 or more a hydrophobic film-forming agents, water, a plasticizing agent, an antifungal agent, and alcohol. Furthermore, Patent Document 5 discloses a formulation which includes a hydrophilic film-forming substance, an antifungal agent, and water.
Furthermore, Patent Document 6 discloses an external composition which includes glycol salicylate in addition to an antifungal agent.
However, among these formulations, patches which include antifungal agents blended in an acrylic or a rubber-base adhesive did not provide sufficient drug release from the formulations or sufficient permeation of the drug into the application sites, resulting in insufficient drug retention on the application sites. In the nail lacquer or nail enamel formulations which include hydrophobic film-forming substances and hydrophilic film component substances, dehydration occurs at the application sites so that films are formed by volatilizing solvents contained in the compositions, resulting in unfavorable irritation. Furthermore, the formulations require the use of solvents or detergents to peel off, and thus they are less convenient.
Furthermore, formulations which include glycol salicylate in order to increase the permeability and retention of antifungal agents in the stratum corneum, for example, ointments, creams, gels, gel creams, and liquid preparations have the problems such as an inadequate therapeutic effect because of poor drug retention in the stratum corneum and short duration of effective drug concentration.
Among other antifungal agents, butenafine hydrochloride, which is a benzylamine antifungal agent, has been so far clinically used in the form of external solutions, creams, ointments, or sprays as therapeutic agents for treatment of dermatomycosis or tinea. However, external aqueous patches including butenafine hydrochloride have not been developed yet.
This is because butenafine hydrochloride has low water-solubility and is difficult to disperse homogeneously in the gel paste of an aqueous patch. Furthermore, as described above, patches which include antifungal agents blended in an acrylic or a rubber-base adhesive do not provide sufficient release of free butenafine as an active ingredient from the formulations or sufficient permeation of free butenafine into the application sites.    [Patent Document 1] Japanese Patent Laid-Open Hei 7-309755    [Patent Document 2] Japanese Patent Laid-Open Hei 7-309756    [Patent Document 3] Japanese Patent Laid-Open Hei 6-211651    [Patent Document 4] Japanese Patent Laid-Open Hei 7-277975    [Patent Document 5] Japanese Patent Laid-Open Hei 10-152433    [Patent Document 6] Japanese Patent Laid-Open Hei 8-20527